Pacemaker activity can be induced in guinea pig, dog, and cat ventricullr myocardial fibers by small depolarizing currents. Induced pacemaker activity occurs at normal temperatures and pH in conventional tyrode solution. Pacemaker rate is slowed by inhibitors of Na and Ca currents including certain antiarrhythmic drugs. If such pacemaker activity occurs in vivo it could be a precipitating or causal factor in clinical arrhythmias, especially those induced by myocardial infarction or accidental electrical shock. I propose to study the phenomenon in terms of a) occurrence in myocardium of guinea pig, dog, and cat; b) occurrence in atrial as well as ventricular and Purkinje tissue; c) specific ionic mechanisms; d) precipitating factors which might interact with the effects of the depolarizing currents such as sympathomimetics, digitalis, and anoxia; e) sensitivity to specific types of antiarrhythmic drugs; f) occurrence under conditions analogous to those obtained in the intact heart after myocardial infarction. The primary technique involved will be transmembrane potential recording from, and voltage clamping of, isolated myocardial preparations in a sucrose gap chamber.